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Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review
Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder. Several male patients with OTCD suffer from severe hyperammonemic crisis in the neonatal period, whereas others develop late-onset manifestations, including hyperammonemic coma. Females with heterozygous pathogenic variants in the...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9593096/ https://www.ncbi.nlm.nih.gov/pubmed/36303552 http://dx.doi.org/10.3389/fgene.2022.952467 |
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author | Kido, Jun Sugawara, Keishin Sawada, Takaaki Matsumoto, Shirou Nakamura, Kimitoshi |
author_facet | Kido, Jun Sugawara, Keishin Sawada, Takaaki Matsumoto, Shirou Nakamura, Kimitoshi |
author_sort | Kido, Jun |
collection | PubMed |
description | Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder. Several male patients with OTCD suffer from severe hyperammonemic crisis in the neonatal period, whereas others develop late-onset manifestations, including hyperammonemic coma. Females with heterozygous pathogenic variants in the OTC gene may develop a variety of clinical manifestations, ranging from asymptomatic conditions to severe hyperammonemic attacks, owing to skewed lyonization. We reported the variants of CPS1, ASS, ASL and OTC detected in the patients with urea cycle disorders through a nation-wide survey in Japan. In this study, we updated the variant data of OTC in Japanese patients and acquired information regarding genetic variants of OTC from patients with OTCD through an extensive literature review. The 523 variants included 386 substitution (330 missense, 53 nonsense, and 3 silent), eight deletion, two duplication, one deletion-insertion, 55 frame shift, two extension, and 69 no category (1 regulatory and 68 splice site error) mutations. We observed a genotype–phenotype relation between the onset time (neonatal onset or late onset), the severity, and genetic mutation in male OTCD patients because the level of deactivation of OTC significantly depends on the pathogenic OTC variants. In conclusion, genetic information about OTC may help to predict long-term outcomes and determine specific treatment strategies, such as liver transplantation, in patients with OTCD. |
format | Online Article Text |
id | pubmed-9593096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95930962022-10-26 Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review Kido, Jun Sugawara, Keishin Sawada, Takaaki Matsumoto, Shirou Nakamura, Kimitoshi Front Genet Genetics Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder. Several male patients with OTCD suffer from severe hyperammonemic crisis in the neonatal period, whereas others develop late-onset manifestations, including hyperammonemic coma. Females with heterozygous pathogenic variants in the OTC gene may develop a variety of clinical manifestations, ranging from asymptomatic conditions to severe hyperammonemic attacks, owing to skewed lyonization. We reported the variants of CPS1, ASS, ASL and OTC detected in the patients with urea cycle disorders through a nation-wide survey in Japan. In this study, we updated the variant data of OTC in Japanese patients and acquired information regarding genetic variants of OTC from patients with OTCD through an extensive literature review. The 523 variants included 386 substitution (330 missense, 53 nonsense, and 3 silent), eight deletion, two duplication, one deletion-insertion, 55 frame shift, two extension, and 69 no category (1 regulatory and 68 splice site error) mutations. We observed a genotype–phenotype relation between the onset time (neonatal onset or late onset), the severity, and genetic mutation in male OTCD patients because the level of deactivation of OTC significantly depends on the pathogenic OTC variants. In conclusion, genetic information about OTC may help to predict long-term outcomes and determine specific treatment strategies, such as liver transplantation, in patients with OTCD. Frontiers Media S.A. 2022-10-11 /pmc/articles/PMC9593096/ /pubmed/36303552 http://dx.doi.org/10.3389/fgene.2022.952467 Text en Copyright © 2022 Kido, Sugawara, Sawada, Matsumoto and Nakamura. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Kido, Jun Sugawara, Keishin Sawada, Takaaki Matsumoto, Shirou Nakamura, Kimitoshi Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review |
title | Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review |
title_full | Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review |
title_fullStr | Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review |
title_full_unstemmed | Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review |
title_short | Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review |
title_sort | pathogenic variants of ornithine transcarbamylase deficiency: nation-wide study in japan and literature review |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9593096/ https://www.ncbi.nlm.nih.gov/pubmed/36303552 http://dx.doi.org/10.3389/fgene.2022.952467 |
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